Heterolytic cleavage catalysis

Potassium peroxodisulphate (K2S2Og) also oxidizes sulphoxides to sulphones in high yield, either by catalysis with silver(I) or copper(II) salts at room temperature85 or in pH 8 buffer at 60-80 °c86-88. The latter conditions have been the subject of a kinetic study, and of the five mechanisms suggested, one has been shown to fit the experimental data best. Thus, the reaction involves the heterolytic cleavage of the peroxodisulphate to sulphur... 

In the field of enzyme catalysis, heme-proteins such as cytochrome P450, for example, exhibit both types of 0-0 bond cleavages in organic hydroperoxides and peroxy acids (178). Heterolytic cleavage of HOOH/ROOH yields H20 or the corresponding alcohol, ROH and a ferryl-oxo intermediate (Scheme 4). Homolytic 0-0 bond cleavage results in the formation of a hydroxyl (HO ) or an alkoxyl (RO ) radical and an iron-bound hydroxyl radical. 

The term acid catalysis is often taken to mean proton catalysis ( specific acid catalysis ) in contrast to general acid catalysis. In this sense, acid-catalyzed hydrolysis begins with protonation of the carbonyl O-atom, which renders the carbonyl C-atom more susceptible to nucleophilic attack. The reaction continues as depicted in Fig. 7. l.a (Pathway a) with hydration of the car-bonium ion to form a tetrahedral intermediate. This is followed by acyl cleavage (heterolytic cleavage of the acyl-0 bond). Pathway b presents an mechanism that can be observed in the presence of concentrated inorganic acids, but which appears irrelevant to hydrolysis under physiological conditions. The same is true for another mechanism of alkyl cleavage not shown in Fig. 7.Fa. All mechanisms of proton-catalyzed ester hydrolysis are reversible. 

Another type of reaction was seen for dalvastatin (8.151), a prodrug that bears an unsaturated side chain. The hydrolysis of dalvastatin to the active acid competes with epimerization at C(6), the rate of the reaction being independent of pH above pH 2 [192], The mechanism is believed to be one of heterolytic cleavage of the C(6)-0 bond to generate a C-centered carbonium ion stabilized by the extended conjugated system characteristic of this compound. In the pH range 2 - 7, the rate of epimerization was found to be ca. 100 times faster than hydrolysis. Above pH 7, base catalysis accelerates hydrolysis, the rate of which increases ca. 100-fold between pH 7 and 9. These facts serve only to complicate the design of HMG-CoA reductase inhibitors and the interpretation of their pharmacokinetic behavior. 

It may be reasonable to argue that this further activation is achieved in several ways. The acid-catalysis required for Gal and de Bruin complex [Rh(/c -bpa)(cod)](PF6) to react with dioxygen can be used to protonate the peroxo compoimd (Scheme 10) to a hydroperoxo species. This is a way to achieve further activation of dioxygen, since it decreases the nucleophilic character of the peroxo hgand and makes interaction with the coordinated olefin easier. Recent works by Moro-oka [88,89] and Braun [90] (Scheme 15) have shown that peroxorhodium complexes can be protonated to hydroperoxo compounds. However, the addition of a second mole of acid leads to hydrogen peroxide ehmination rather than to the highly electrophilic oxo species (M = O) that could result from the heterolytic cleavage of the O - O bond with removal of water. 

However, several observations of note were made. First and foremost was that H2 was necessary for catalysis. This fact is not incorporated into the catalytic cycle usually cited (Scheme 7), but rather, H2 is considered to be involved only in activating the precursors. Reduction of Ru(III) (and higher valent species) to Ru(II) is known to be preceded by heterolytic cleavage of H2 (79,80), and under the anhydrous conditions of the system, it is possible that H2 is constantly necessary to maintain the ruthenium in a lower oxidation state (the catalytic cycle may generate an otherwise inactive high-valent species, either directly or by some side reaction). The presence of H + and an iodide promoter is also requisite for reactivity. It has also been concluded that for catalysis, the I/Ru ratio must equal or exceed 3 (73, 78). 

Reactions with H2O2 may be divided into two classes arising from the homolytic vy. heterolytic cleavage of the 0-0 bond (173). In homolytic catalysis, the oxygen-centered radicals are intermediates the participation of concerted processes in heterolytic catalysis precludes paramagnetic intermediates. Product selectivity is usually higher in the latter class. Transition metal cations in low oxidation states, such as Cu, Ti, Cr, and Fe " ", catalyze the homolytic... 

A typical example of the microdielectric catalysis by cyclodextrins is the decarboxylation of anions of activated acids such as a-cyano and y8-keto acids [15]. These reactions proceed unimolecularly via rate-determining heterolytic cleavage of the carbon-carbon bond adjacent to the carboxylate group (Scheme 3). 

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